How Congress Ignored Science and Fueled Antibiotic Resistance

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How Congress Ignored Science and Fueled Antibiotic Resistance

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The gray clapboard house on the two-lane road in a western suburb of Boston looked, in the fall of 1974, the way you would expect a comfortable old Massachusetts house full of children to look. It was rambling and tall, made out of a house and a barn butted together. There were other barns out back, down a long gravel drive that stretched to a grove of trees: small sheds and one big building, 200 feet on the long side, painted an iconic barnyard red. There was a milk cow, a few horses, a couple of pigs, and chickens: white laying hens, some in a chalet-shaped coop and some skittering underfoot between the trees.

Inside the house, kids were everywhere, seemingly as much underfoot as the chickens were: Richard, Mary, and the twins (Peter and Paul); Steve, Ronnie, and Mike; Christopher, Christine, and Lisa. Their parents, Richard and Joan Downing, were Catholic and had wanted a big family. Richard had done well in business, establishing credit-reporting firms around Boston. When the twins turned out to be their last biological children, he and Joan had committed to using their money to improve other kids’ lives, so there were always extra children in the house, up to a dozen at a time.

Some stayed a few months or years as fosters; others joined the family permanently through adoption. The Downings were sturdy people, no-nonsense but warm. Their house was mostly happy chaos, with kids racing around corners clutching sports equipment and homework, and dashing outside to feed the pigs and milk the cow.

Excerpted from Big Chicken: The Incredible Story of How Antibiotics Created Modern Agriculture and Changed the Way the World Eats by Maryn McKenna.

National Geographic Books

There was just one note of stern discipline, in a notice stuck on the front of the refrigerator. It had been written by Mary, the oldest daughter, in the careful printing she was learning in college biology. It said, in block letters, “No Juice Until I Get Your Poop.”

Inside the refrigerator, along with celery and cold cuts and the much desired juice, were a couple of brown paper lunch bags. All of the bags held the same thing: a cluster of long, clear tubes, tightly capped, each one holding swabs that looked like long Q-tips. Each of the swabs was stained at one end. The swabs in one bag came from the Downing kids. The swabs in another came from the neighbors, who dropped them off once a week. (They didn’t wait for juice.) The swabs in the third had been swirled over the butts of chickens in the big barn at the back.

It looked like arrangements for a kid’s jokey science fair exhibit, but this endeavor was deadly serious. The Downings had agreed to host an experiment, one that centered on the animals out back and involved their sprawling family and their neighborhood. The experiment was the first attempt to explore, in an organized, documented way, that antibiotics given routinely to animals represented a threat to human health.

Actually, at first, it intended to disprove it. The sponsors of the study were industry: the Animal Health Institute, the trade group representing the companies that made and sold antibiotics used on farms. At this point, antibiotics to promote animal growth were a routine component of agriculture: 40 percent of the ones made in the United States were going into livestock, not to human patients. But it was also 10 years since scientists had begun claiming a connection between farm antibiotic use and human illness, and growth promoters and preventive dosing were coming under increased public scrutiny. The animal drug industry was under pressure to prove its products were safe, and it had agreed to fund a study to demonstrate that.

The study would not go the way the industry hoped, and it would change the debate about agricultural antibiotic use for good.

Meet the Downings

The study was being conducted by Dr. Stuart B. Levy, a researcher in Boston. Levy was 36 in 1974. He was the son of a family doctor from Delaware and had grown up accompanying his father on house calls and discussing cases afterward. He was a faculty member at Tufts University School of Medicine, in a part of Boston that is gentrified now but was cheap and seedy then, and he had taken a circuitous route to get there, studying first literature, then medicine, and then microbiology in Italy and France.

Researchers had confirmed an earlier discovery that genes conferring antibiotic resistance could stack up and be carried from one bacterium to another. That would allow an organism to acquire resistance in advance of ever being exposed to a drug, while also allowing multiple types of resistance to spread. It threatened to make resistance much harder to track and combat.

about the author

About

Maryn McKenna is an award-winning journalist and author specializing in public health and food policy. McKenna is the author of two previous books, Superbug and Beating Back the Devil. She is a former WIRED contributing writer.

The Animal Health Institute found Levy and offered to fund a study on behalf of farm antibiotics. That was why there were tubes of poop-stained sample swabs in the Downings’ refrigerator. They were tools that would help Levy establish, or disprove, whether resistance could migrate through the environment, from animals that had received antibiotics, to animals and people who had not. Growth promoters’ proponents hoped the answer would be no.

Levy didn't know the Downings, but he knew what he needed to make the proposed study possible: a place that looked like a farm but had not been functioning as one. He needed new animals that had never received antibiotics, a place to raise them where antibiotics had not been used in the recent past, and a group of animal handlers numerous enough to conduct the experiment and healthy enough to not be taking antibiotics themselves. For bonus points, the location needed to be close enough to his office that he and his staff could travel back and forth affordably. In the affluent suburbs of Boston, that was a complex order to fill. He was not sure even where to look, but he began to ask around. Boston’s rural exurbs are very unlike the city, but so many people commute in and out that they are more tightly tied than they look. The news of Levy’s search for a place to conduct his study percolated through the medical community, and after a while, someone got in touch: a veterinarian responsible for the mice and other animals that Massachusetts General Hospital kept to do research. He lived in the tiny town of Sherborn, 20 miles southwest of Boston. His across-the-street neighbors were a relaxed, irreverent family; they had lots of kids; and they lived on a big parcel with a couple of barns that had once been an egg-sorting business. He offered to make an introduction.

Levy drove out to meet the Downings. He described what he envisioned: a temporary farm housing 300 chickens, to be maintained for at least a year. Richard Downing liked the impish, focused physician, and he liked the idea of contributing to knowledge and letting his kids watch an experiment up close. But he had grown up on a poultry farm, in the coastal town of Weymouth, and he knew Levy did not know how to accomplish what he wanted to do.

“I told him he was crazy—he had no idea what this would take,” Downing recalls. “He’d have to build the pens, buy the feed, set up the watering system, put in heat, find someone to look after them, get someone to clean up. And he said I was right, and he hoped we could help.”

Within two weeks, 90 percent of the chickens were pooping out resistant bugs.

The Downings accepted the challenge—for fun and out of curiosity, and because being unconventional had never worried them before. To manage the experiment, they nominated their oldest daughter, Mary. A sophomore at a local college, she was living at home to save money. She wanted to go to France after graduation, but with so many other kids in the household, spare funds were in short supply. She and her parents and Levy struck a deal. She would supervise the chickens, water and feed them, and collect all the data Levy would need, which, she learned, meant collecting poop, and not just from the birds. He offered to pay her $50 every week, about $250 now. She signed on.

In the big barn at the back of the property, Levy and 10 medical students, along with the Downings and their kids, built six wire pens, each equipped with gas heaters and independent food trays and water systems. Four were inside the barn, 50 feet apart; two more stood outside its thick timber walls. Then Levy went in search of chicks. To ensure there would be no contamination, nothing in the chickens’ systems that would slant the study results, he bought them from a company that supplied “pathogen-free” eggs to laboratories.

In July 1974, the day-old Leghorn chicks arrived in Sherborn and were stashed in one of the pens with a heat lamp and water and antibiotic-free food. When they were two months old, the experiment began. Levy divided the chicks into six batches, 50 per pen. At the local feed store, he bought two types of feed, one antibiotic free and another that was sold premixed with antibiotics. It contained oxytetracycline in a ratio of 100 grams per ton. Half of the birds, in three of the six pens, got the drug-free feed. The other half got the tetracycline-laced mix. Levy had several questions to answer. First, did the antibiotics in feed cause resistant bacteria to emerge or multiply in the chickens receiving it? Second, did that resistance cross from those chickens to the rest of the flock? And third and most crucial, could it make the leap from chickens to humans?
For the experiment to establish everything that Levy planned, he needed to recruit people beyond the Downings to participate. At their invitation, he drove out to meet the neighbors. Joan and Richard threw a barbecue and invited the five families—10 parents, 14 kids—who lived up and down the road. After the hamburgers and hot dogs and corn were handed around, the Downing boys rolled a washtub over to make a podium. Levy had discussed with the parents what he planned to say, and they had reassured him that it was best to be straightforward. Still, he felt a little nervous as he climbed up on the tub.

“We’re asking you all to be part of an experiment,” he told the guests. The parents made murmurs of interest and shushed their kids. He described the puzzle of antibiotic resistance, how the chickens might help solve it, and that the Downings had agreed to assist. Then he got to the hard part.

“We’d like you to donate something that you have to science,” he said. The small crowd perked up with curiosity. He heard one woman say, “This is exciting!”

He took a deep breath. “Frankly,” he said, “we need your shit.” The silence was deadly. Then three-year-old Lisa scrambled up, round-eyed. “You want our poops?” she squeaked. That broke the ice. Everyone laughed, and they all agreed to help; none of the families backed out. And that in turn justified Mary’s substantial pay for managing the experiment. Her job was not just feeding and watering the chickens and swabbing their butts every seven days; it was also persuading and bugging and nagging her siblings and the neighbor kids, and her parents and the neighbor parents, to do their sampling duty. Every week, the Downings’ refrigerator shelf filled up with bags full of tubes, and then emptied again when Levy’s staff picked them up.

The results came quickly. Samples taken before the experiment began showed that very few bacteria in the guts of the chickens, family, and neighbors possessed genetic defenses against tetracycline. That was to be expected, given the random roulette of mutation. But once the drug-laced feed was administered, those bacteria multiplied in the birds harboring them and spread to birds that had started out clean. The first changes appeared in 36 hours, and within two weeks, 90 percent of the chickens were pooping out resistant bugs. The dose of antibiotics in the feed had killed the gut bacteria vulnerable to the drug but did not harm the ones that were protected by minor mutations—and those resistant survivors thrived and multiplied in the living space left empty when the other bacteria were killed. Researchers had assumed this was what occurred in animals given antibiotics, turning them into factories for producing resistant bacteria. But no one had measured it in the wild before, and no one had expected to see it happen so fast.

For a few weeks, the chickens getting drug-free feed remained clean of resistant bugs. Then things changed. First, the bacteria from the chickens getting the antibiotic-laced feed became resistant to multiple drugs—sulfas, chloramphenicol, streptomycin and neomycin, and two derivatives of penicillin—even though the feed contained only tetracycline. Then the multidrug-resistant bacteria appeared in the chickens that had never received that feed and had no contact with the birds that did. And soon after, the same multidrug-resistant bacteria showed up in the Downings’ poop as well.

The route they traveled was not obvious. The groups of chickens were never let out of their pens or allowed to mingle. If any birds managed to escape, Mary took them out of the study to a coop on the other side of the property. When she fed and watered and tested the chickens, she moved through the barn in a precise pattern, going to the drug-free birds first and washing her hands and changing boots after each pen. And the Downings were not eating the experimental chickens (though they did have a giant barbecue once the study was done).

To the disappointment of his sponsors, Levy had demonstrated what they hoped to disprove. Even though the feed contained just tiny doses of antibiotics, those doses selected resistant bacteria—which not only flourished in the animals’ systems but left the animals, moved through the farm’s environment, and entered the systems of other animals and of humans in close proximity. (But not in any of the neighbors, who were the experiment’s control group; the resistant bacteria did not spread to them.) The altered bacteria were an untrackable form of pollution. And because they could accumulate resistance genes invisibly, they were an unpredictable threat as well.

There was one footnote to what Levy had found, and for years it would influence efforts to control farm antibiotic use: The Downings had not gotten sick. There are many strains of E. coli, and the one that resided in the chickens’ guts and crossed to their owners was not a disease-causing one. Instead, it was a commensal, one of the range of benign bacteria that occupy the gut and pervade the world without causing illness. On the scientists’ side, this did not diminish the risk; it only made the bacterial traffic more complicated. But it would allow those who chose not to believe in the threat to downplay the danger.

Dirty Politics

Levy published his description of what happened on the Downings’ farm in September 1976. In April 1977, the new commissioner of the FDA—Donald Kennedy, in office just two weeks—stood up at a meeting and dropped a bombshell: The US government would ban growth promoters from American agriculture. Kennedy was 46, a slender man in big glasses who vibrated with impatient energy. He was a biologist, had a PhD from Harvard, and had become a department chair at Stanford University when he was only 34. Stanford had loaned him to the White House, and he had been working there part time since the beginning of 1976, helping the administration of President Gerald Ford set up the new Office of Science and Technology Policy.

Late in 1976, little-known former Georgia governor Jimmy Carter squeaked past Ford in a close election, positioning himself as an outsider who could cleanse the country of the scandal of Watergate and the lingering taint of the Vietnam War. Carter brought a crew of earnest young reformers with him. The FDA was high on their agenda. It needed a leader who could speak up for science and owed no favors to the Washington power structure. Donald Kennedy fit. The White House expected him to be bold.

But maybe not as bold as he turned out to be. On his first visit to the FDA’s National Advisory Food and Drug Committee, a group of scientists and industry representatives who for months had been fractiously debating farm antibiotic use, Kennedy made it clear the discussion was over. In a short statement, he announced that his department would immediately ban any growth promoter use of penicillin and the tetracyclines, and it would also ban preventive use as soon as researchers could identify compounds that farmers could use instead. Henceforth, he added, the drugs would be used in animal feed only if a veterinarian wrote a prescription for them.

“The benefit of using these drugs routinely as over-the-counter products to help animals grow faster or in prophylactic programs does not outweigh the potential risks posed to people,” Kennedy said. “Although we can point to no specific instance in which human disease is more difficult to treat because drug resistance has arisen from an animal source, it is likely that such problems could have gone unnoticed.”

Kennedy was a scientist, accustomed to weighing evidence; in the language he spoke, potential and likely had weight. But the politicians who were his audience did not receive what he said as proof. They heard it as a supposition, and also as a threat, to an enormous industry with outsize political influence. By this point, almost every food animal raised in the United States was receiving antibiotics sometime in its life: close to 100 percent of the chickens and turkeys, 90 percent of veal calves and swine, 60 percent of cattle.

“There are no widespread epidemics of untreatable disease among humans because of antibiotics in livestock feeds,” insisted a representative of American Cyanamid.

Within weeks, Kennedy was hauled before Congress and vilified, beginning a series of hostile hearings that would go on for months. His proposal to take away growth promoters—and place all antibiotic use under the control of veterinarians—was “totally unworkable,” according to the American National Cattlemen’s Association. It “could jeopardize nearly any product employed in animal agriculture,” the Animal Health Institute fumed. “There are no widespread epidemics of untreatable disease among humans because of antibiotics in livestock feeds,” insisted a representative of American Cyanamid. The Southeastern Poultry and Egg Commission said forgoing the drugs would cost egg producers $4.25 million. Practically spitting in derision, the director of the Northeastern Poultry Producers Council snarled, “The Commissioner’s logic would eventually lead to a government edict to abort all pregnant women because every aspect of life—every minute of every day—poses some potential risk to health.”

Kennedy and his staff ignored the condemnation. On August 30 and October 21, the FDA filed two lengthy documents in the Federal Register describing their case against growth promoters: one for penicillin, one for the tetracyclines. Technically the documents were “notices of opportunity for a hearing,” inviting the drugs’ manufacturers to request an appearance to defend their drugs. But in practical terms, they were legal briefs: precisely footnoted arguments that built the case against growth promoters, piece by piece. And like any good brief, they made clear who the defendants were. For each drug category, the notices listed the products at stake. There were 26 containing penicillin and 31 for the tetracyclines, and they came from almost all the major pharmaceutical and animal feed manufacturers in America.

A message was passed from Congress up to the White House and then down to Kennedy: The hearings would not be allowed to happen. Representative Jamie Whitten, a Mississippi Democrat who since 1949 had chaired the body where the FDA’s budget originated—the House Appropriations Subcommittee on Agriculture and Rural Development, the fount of farm pork-barrel funding—had vowed to hold that budget hostage if Kennedy proceeded. If he did, it would put at risk other reforms the Carter administration had planned.

The White House brokered a deal. Whitten’s agricultural contacts were insisting there were gaps in the evidence; he wanted to see them filled. If Kennedy abandoned the attempt to ban growth promoters, Whitten would not kidnap the FDA’s budget. In fact, he would add some extra money, enough to allow the FDA to do the study his allies were asking for. In 1978, he approved enough funds to allow the National Academy of Sciences to study the public health impact of growth promoters. The appropriation allowed enough money for three years of research.

Coincidentally, Kennedy was due back at Stanford within two years, at the end of the leave it had granted him to work in government. It might have seemed that Whitten was just kicking the can down the road, until the arrival of Kennedy’s successor at the FDA.
But the old Southerner had been a politician for as long as Kennedy had been alive, and he was craftier than that. Whitten added a rider to the next appropriations bill: Until a study answered the question of public health harm to his personal satisfaction, the FDA would not be allowed to act on any antibiotic bans. There would be dozens of studies over the years and eventually hundreds.

None would be good enough. Whitten renewed the rider every year until he retired in 1995. Whitten’s obstinacy on behalf of agriculture cemented the security of farm antibiotic use in the United States. The United States let growth promoters and preventive dosing flourish unregulated. More and more evidence— which is to say, larger, deadlier outbreaks—would accumulate for decades before anyone found the courage to try to control farm antibiotics again.

Excerpted from Big Chicken by Maryn McKenna; published by National Geographic Partners on September 12th, 2017. Available wherever books are sold.

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